Falk P G, Hooper L V, Midtvedt T, Gordon J I
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Microbiol Mol Biol Rev. 1998 Dec;62(4):1157-70. doi: 10.1128/MMBR.62.4.1157-1170.1998.
Studying the cross talk between nonpathogenic organisms and their mammalian hosts represents an experimental challenge because these interactions are typically subtle and the microbial societies that associate with mammalian hosts are very complex and dynamic. A large, functionally stable, climax community of microbes is maintained in the murine and human gastrointestinal tracts. This open ecosystem exhibits not only regional differences in the composition of its microbiota but also regional differences in the differentiation programs of its epithelial cells and in the spatial distribution of its component immune cells. A key experimental strategy for determining whether "nonpathogenic" microorganisms actively create their own regional habitats in this ecosystem is to define cellular function in germ-free animals and then evaluate the effects of adding single or several microbial species. This review focuses on how gnotobiotics-the study of germ-free animals-has been and needs to be used to examine how the gastrointestinal ecosystem is created and maintained. Areas discussed include the generation of simplified ecosystems by using genetically manipulatable microbes and hosts to determine whether components of the microbiota actively regulate epithelial differentiation to create niches for themselves and for other organisms; the ways in which gnotobiology can help reveal collaborative interactions among the microbiota, epithelium, and mucosal immune system; and the ways in which gnotobiology is and will be useful for identifying host and microbial factors that define the continuum between nonpathogenic and pathogenic. A series of tests of microbial contributions to several pathologic states, using germ-free and ex-germ-free mice, are proposed.
研究非致病生物体与其哺乳动物宿主之间的相互作用是一项实验挑战，因为这些相互作用通常很微妙，而且与哺乳动物宿主相关联的微生物群落非常复杂且动态变化。在小鼠和人类的胃肠道中维持着一个大型的、功能稳定的微生物群落。这个开放的生态系统不仅在微生物群组成上存在区域差异，而且在上皮细胞分化程序及其组成免疫细胞的空间分布上也存在区域差异。确定“非致病”微生物是否在这个生态系统中积极创造自身区域栖息地的一个关键实验策略是，先在无菌动物中定义细胞功能，然后评估添加单一或几种微生物物种的效果。这篇综述聚焦于悉生生物学（即对无菌动物的研究）如何以及需要如何用于研究胃肠道生态系统是如何形成和维持的。讨论的领域包括利用可进行基因操作的微生物和宿主来创建简化生态系统，以确定微生物群的组成部分是否积极调节上皮细胞分化，从而为自身和其他生物体创造生态位；悉生生物学有助于揭示微生物群、上皮细胞和黏膜免疫系统之间协同相互作用的方式；以及悉生生物学在识别界定非致病和致病之间连续统一体的宿主和微生物因素方面的应用方式及未来用途。本文还提出了一系列使用无菌小鼠和无菌后小鼠来测试微生物对几种病理状态影响的实验。
